British Journal of Anaesthesia 109 (2): 144–54 (2012)

Advance Access publication 26 June 2012 . doi:10.1093/bja/aes214

REVIEW ARTICLES

Failed epidural: causes and management

J. Hermanides, M. W. Hollmann*, M. F. Stevens and P. Lirk
Department of Anaesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
* Corresponding author. E-mail: m.w.hollmann@amc.uva.nl

Summary. Failed epidural anaesthesia or analgesia is more frequent than generally

Editor’s key points
† Inadequate anaesthesia or
analgesia with an epidural may
be common.
† There are technical (equipment,
anatomy) and pharmacological
(drugs, doses) causes.
† The use of adjuvants appears to
increase the success rate.
† Postoperatively, the use of
patient-controlled epidural
anaesthesia with background
infusion appears most effective.
recognized. We review the factors known to influence the success rate of epidural
anaesthesia. Reasons for an inadequate epidural block include incorrect primary
placement, secondary migration of a catheter after correct placement, and
suboptimal dosing of local anaesthetic drugs. For catheter placement, the loss of
resistance using saline has become the most widely used method. Patient
positioning, the use of a midline or paramedian approach, and the method used
for catheter fixation can all influence the success rate. When using equipotent
doses, the difference in clinical effect between bupivacaine and the newer isoforms
levobupivacaine and ropivacaine appears minimal. With continuous infusion, dose
is the primary determinant of epidural anaesthesia quality, with volume and
concentration playing a lesser role. Addition of adjuvants, especially opioids and
epinephrine, may substantially increase the success rate of epidural analgesia.
Adjuvant opioids may have a spinal or supraspinal action. The use of patient-
controlled epidural analgesia with background infusion appears to be the best
method for postoperative analgesia.
Keywords: epidural, analgesic techniques; extradural, anaesthetics local

In contrast to the subjective experience of many anaesthe-
tists, failure of epidural anaesthesia and analgesia is a fre-
quent clinical problem. Current estimates of the incidence
of failed epidurals are hampered by the lack of a uniform
outcome measure. The definitions given cover a spectrum
ranging from insufficient analgesia to catheter dislodgement
to any reason for early discontinuation of epidural analgesia
(Table 1). In a heterogeneous cohort of 2140 surgical
patients, failure rates of 32% for thoracic and 27% for
lumbar epidural were described.1 Of note, active manage-
ment of inadequate epidural anaesthesia, including a new
block, results in an almost complete success rate.2 In an
imaging study of failed epidurals, incorrect catheter place-
ment accounted for half of the failures, while the remaining
patients experienced suboptimal analgesia through a cor-
rectly positioned catheter.3 A flow chart illustrates the prob-
lems encountered during epidural anaesthesia using the
example of a Caesarean section, ultimately resulting in a
success rate of just 76% (Fig. 1).
This review summarizes technical factors known to
influence block success, and gives an overview of the pharma-
cological strategies available to optimize epidural anaesthesia
and analgesia. For each section, we performed a comprehen-
sive literature search for full published reports in MEDLINE cov-
ering manuscripts up to October 2011, with reference lists of
retrieved articles searched for additional trials or reports. We
ranked meta-analyses and randomized controlled trials
(RCTs) highest, with other trials and reports resorted to in
case no broad evidence base could be discerned.
Technical factors influencing block success
Anatomical catheter location
Epidural catheters may primarily be placed incorrectly, or
become dislodged during the course of treatment. Transfor-
aminal migration of the catheter tip and asymmetric
spread have been described during epidural analgesia.4
Primary misplacement of epidural catheters in the paraver-
tebral space, in the pleural cavity, and intravascularly has
been described. Even when the epidural space is correctly
identified, the catheter will not necessarily follow a straight
line when being advanced. The epidural catheter may leave
the epidural space through an intervertebral foramen at
levels above or below the insertion site (Fig. 2). In a group
of obstetric patients, failure of epidural analgesia after
initial success was observed in 6.8%.2 Secondary migration
of the catheter after successful initial placement can occur.
During normal patient movement, epidural catheters may
be displaced by centimetres.5 In 60 patients undergoing
lung surgery with a thoracic epidural, with chest radiographs
taken before and after operation, the catheter had migrated
more than one vertebral level in 24%. In addition to body

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Epidural anaesthesia BJA

Table 1 Definitions and rates of failed epidural anaesthesia or analgesia. *Pre-intervention group in an intervention study

Type of surgery Failure definition Failure rate Thoracic/lumbar

Eappen and Parturients receiving epidural Any reason requiring catheter replacement 550/4240 Lumbar
colleagues97 analgesia or anaesthesia for delivery after the catheter was secured to the back (13.1%)
with adhesive tape, a greater than three
dermatomal segment discrepancy
between analgesic level as assessed by
temperature (ice) sensation in a patient
complaining of pain after the initial bolus
of epidural bupivacaine
Ready1 All surgical patients Any condition during the course of treatment n¼2140; Thoracic:lumbar
that requires epidural catheter replacement or thoracic (32%); ?:?
the addition of another major treatment lumbar (27%)
modality such as i.v. patient-controlled
analgesia
McLeod and Major oesophageal, gastric, small Apparent inability to deliver local anaesthetic/ 83/640 (13.0%) Thoracic
colleagues98 and large bowel surgery, and aortic opioid solution to the epidural space due to
aneurysm repair occlusion, dislodgement, or leakage, or poor
spread within the epidural space resulting in
patchy or unilateral block
Rigg and Major abdominal operations or Could not be inserted, removed before leaving 203/431 Thoracic:lumbar
colleagues22 oesophagectomy operating theatre, removed before 72 h (47.1%) ?:?
Neal90 Oesophagectomy Catheter dislodgement 8/46 (14.2%) Thoracic
Pan and Obstetric neuraxial analgesia Epidural or CSE procedures resulting in 1099/7849 Lumbar
colleagues2 and anaesthesia inadequate analgesia or no sensory block after (14%)
adequate dosing at any time after initial
placement, inadvertent dural puncture with
the epidural needle or catheter, i.v. epidural
catheter, or any technique requiring
replacement or alternative management
Motamed and Major elective abdominal surgery Interruption of epidural analgesia before 48 h 31/125 (24.8%) Thoracic
colleagues3 for cancer for any reason. A VAS score that exceeded 30
mm at rest and persisted for 45 min after a
rescue 5 ml epidural 0.125% bupivacaine
injection and 1 g paracetamol i.v. were
administered
Pratt and Pancreatoduodenectomy Aborted before anticipated (fourth 49/158 (31.0%) Thoracic
colleagues99 postoperative day) because of haemodynamic
compromise, inadequate analgesia, or both
Kinsella100 Anaesthesia for Caesarean section Loss of cold sensation, using ethyl chloride 302/1286 Thoracic:lumbar
spray, from T4 (the nipples) down to S5 (the (23.5%) ?:?
buttocks), and also anaesthesia (no feeling)
to a 19 G needle inserted at several points
along the line of surgical incision at T12
Konigsrainer Thoraco-abdominal surgery, upper Motor weakness, catheter dislodgement, 124/300* Thoracic:lumbar
and abdominal surgery, colorectal insufficient analgesia (41.4%) 241:59
colleagues35 surgery, and other

movements, changes in epidural pressure and cerebrospinal
fluid (CSF) oscillations can contribute to the displacement
of epidural catheters.6 The epidural space is a compartmen-
talized and complex structure,7 which may influence cath-
eter placement. Midline fat pedicles may form a barrier to
the spread of local anaesthetics.7
Patient position
Patient positioning potentially affects needle placement by
changing the relationship of osseous and soft tissues. In
addition to the obvious opening of the posterior interlaminar
space by spinal flexion, the position of spinal contents is
altered. The position of the spinal cord within the spinal
canal is not precisely predictable using measures such as
sex, weight, or height. The patient assuming a flexed position
with the head down will result in the anterior movement of
the spinal cord at the thoracic level, while the spinal cord
and cauda equina will be more posterior at the lumbar
level.8 The spinal cord is flexibly attached within the dural
sac, and changes position according to gravity when subjects
are positioned supine, or laterally.9

145
BJA Hermanides et al.

Epidural – 1286

LA did not go in correct space or Other anaesthesia:

change of approach 13
GA for high epidural 1
GA 1

Epidural site leaking 1 RA 9 (of whom 1 then had GA)

1273
Test dose produced block; ? spinal 1

Epidural achieved – 1275 (99%)

Inadequate block after top-up 177 Other anaesthesia:

GA 39
RA 91 (of whom 8 then had GA)
Surgery started with
1098
inadequate block 47

Surgery started with epidural – 1145 (89%)

Inadequate anaesthesia pre-delivery 70 GA 18

Severe pain 27
Mild pain 22
Discomfort 3

Inadequate anaesthesia post-delivery 91 GA 6

(onset after delivery) Severe pain 32
Mild pain 52
Discomfort 1

Successful epidural – 984 (76%)

Fig 1 Regional anaesthesia failure in 5080 Caesarean sections; adapted with permission from Kinsella.100

The sitting position has been described to result in shorter
insertion times and a trend towards higher accuracy at the
first attempt than the lateral position, but at the cost of
more vagal reflexes, and with comparable final success
rates.10 In combined spinal –epidural anaesthesia for Caesar-
ean section, no differences were reported for insertion
times,11 while another study found more technical difficulties
in the lateral compared with the sitting position.12 Lateral
positioning increases the distance from the skin to the epi-
dural space.13 The sitting position leads to epidural venous
plexus distension,14 which may theoretically increase the
risk of vascular puncture, especially in parturients.15
Puncture site
It is known that anaesthetists tend to be inaccurate when
determining the precise dermatomal level for neuraxial
puncture.16 Of note, most studies show that there is a ten-
dency for the site to be more cranial than intended. Suitable
block levels and anatomical landmarks for various types of
surgery are suggested in Table 2.
Midline vs paramedian
There have been few studies comparing the midline and
paramedian approach on block success. In cadavers, using

146
Epidural anaesthesia BJA

Fig 2 Epidural catheter exhibiting through the transforaminal passage; reproduced from Hehre and colleagues with permission.17

in most studies, while differences are likely to exist between

Table 2 Landmarks for epidural anaesthesia and analgesia the thoracic and lumbar levels, for example, one study
reported inability to localize the thoracic epidural space in
Desired dermatome level of neuraxial block
13 out of 447 (2.9%) attempts.22
Type of Upper Anatomical Optimal Correct placement obviously requires correct identification
surgery dermatomal landmark insertion of the epidural space. A variety of methods are used to
block level point
confirm epidural needle position.23 The loss of resistance
Oesophagus, T1 Below T6 –7 (LoR) using saline has become the most widely used
lung clavicle
method, while LoR to air and the hanging drop technique
Upper T1 Below T9 –10
are less widely used.23 A meta-analysis in 2009 included
abdomen clavicle
five RCTs comparing LoR with saline vs air: four in the obstet-
Lower T6 Distal T9 –10
abdomen sternum ric population and one in a general patient population, with a
Caesarean T4 Nipples L4 –5 total of 4422 patients. No significant difference in any
delivery outcome was found, other than a 1.5% reduction in post-
Lower limb L1-2 Inguinal L4 –5 dural puncture headache when using saline.24 A study com-
crease paring combined spinal–epidural punctures using air or
saline found no difference in the success rate or adverse
events.25 A recent retrospective study of 929 obstetric epi-
durals found that when using air for LoR, significantly more
epiduroscopy, paramedian catheters were observed to cause
attempts were needed compared with using saline, with
less epidural tenting, and pass cephalad more reliably than
comparable final success rates.26 Subgroup analyses
midline catheters.18 In patients, faster catheter insertion
showed that the use of the ‘preferred technique’ (i.e. the
times were reported in the paramedian, and higher incidence
technique used by a practitioner .70% of the time) resulted
of paraesthesia in the midline group.19 Adequate local infil-
in significantly fewer attempts, a lower incidence of paraes-
tration is a prerequisite for patient comfort during parame-
thesia, and fewer dural punctures, irrespective of whether
dian puncture.20 21 The paramedian approach may be less
saline or air was used for LoR.26
dependent upon spine flexion.21 The risk of vascular puncture
The hanging drop technique depends on negative pres-
during epidural catheter placement was not associated with
sure within the epidural space. Recent experimental evidence
lumbar midline or paramedian technique in parturients,20
suggests that negative pressure is poor at reliably detecting
while another study suggested more paraesthesia and
the epidural space, and if at all, the hanging drop technique
bloody puncture in non-pregnant adults when the midline
is useful only in the sitting position.27 Of note, identification
approach was used.21
of the epidural space was reported at 2 mm deeper for the
hanging drop when compared with LoR, possibly indicating
Localization of the epidural space increased risk of dural perforation.28 Whichever technique
Inability to correctly insert an epidural catheter at the first is used, it is important to realize that the ligamentum
attempt and the number of attempts required is not reported flavum is not continuous in all patients, and the presence

147
BJA
of midline gaps may make the LoR to needle advancement
and injection of air/saline less perceptible when the midline
approach is used.29
A number of technical aids for epidural anaesthesia have
been described, but none of them have sufficient accuracy
and practicability to justify the increased effort and cost of
their routine use in adults. Ultrasound is a useful educational
tool and can enhance the learning curve for epidural anaes-
thesia.30 Ultrasound pre-assessment of lumbar epidural
space depth has been shown to correlate well with actual
puncture depth in obese parturients.31 In children, ultra-
sound allows for the identification of neuraxial structures,
particularly in neonates. Below an age of 3 months, only
the vertebral bodies are ossified, enabling detailed visualiza-
tion of spinal structures. After 3 months, ossification of the
vertebral column leads to decreased visibility. By the age of
7 yr, visibility of the neuraxial structures, especially the thor-
acic segments, is significantly reduced and comparable with
that of young adults.32 Despite apparently obvious advan-
tages of ultrasound-guided epidural anaesthesia in children,
only one RCT has been conducted, and it found that the use
of ultrasound led to less bony contact, a shorter time to block
success, and decreased supplemental opioid requirements.33
Recently, visualization of epidural spread of local anaesthetic
has been used to predict optimal individual epidural dose.34
Catheter insertion and fixation
The catheter should be inserted at least 4 cm into the epi-
dural space,5 and a recent study reported a higher success
rate with more than 5 cm.35 Tunnelling the epidural catheter
for 5 cm in a cohort of 82 patients was associated with less
motion of the catheter, but the percentage of catheters
maintaining original position was not statistically different.36
In more than 200 patients undergoing either thoracic or
lumbar epidural anaesthesia, tunnelling led to significantly
decreased catheter migration, with a modest clinical net
result of 83% of functioning catheters after 3 days, when
compared with 67% without tunnelling.37 Suturing of the
epidural catheter was similarly associated with less migra-
tion, but at the cost of increased inflammation at the
puncture site.38 Whereas erythema at the puncture site
was not associated with bacterial colonization in small-scale
studies,39 one larger study described a positive correlation.40
In a retrospective observational study of .500 children, tun-
nelling a caudal epidural catheter reduced the risk of bacter-
ial colonization to levels comparable with untunnelled
lumbar catheters.40 These results may be related to the
fact that tunnelling places the catheter entry point above
the diaper in babies and toddlers and may not be
easily transferred to an adolescent population undergoing
lumbar or thoracic epidural anaesthesia. It seems prudent,
however, to consider tunnelling caudal epidural catheters
in babies and toddlers. For lumbar and epidural catheters,
the advantages are less obvious and the need to prevent dis-
lodgement must be weighed against the increased incidence
of erythema at the puncture site, potentially linked to
148
Hermanides et al.
increased risk of bacterial colonization. Catheter fixation
devices are available which may significantly reduce migra-
tion percentage and reduce rates of analgesic failure.41
Unfortunately, there are no studies comparing modern
dressing devices with tunnelling techniques with respect to
migration, analgesic failure, or infection.
Test dose
The best pharmacological way to determine correct place-
ment of an epidural catheter is unclear. A test dose is
given with the two main objectives of detecting intrathecal
or intravascular catheter placement. The optimal strategy
to detect intrathecal catheter placement was long consid-
ered to be lidocaine with epinephrine. Specific regimens
to detect intravascular catheter position have been advo-
cated for non-pregnant adult patients (fixed epinephrine
test dose), parturients (fentanyl test dose), and children
(weight-adjusted epinephrine test dose).42 It is of note
that a non-significant increase in heart rate (,15%) does
not guarantee correct position. Furthermore, patients sensi-
tive to intravascular epinephrine (parturients, patients with
cardiac or vascular disease) may experience undesirable
side-effects if the test is positive. However, this risk is
most likely outweighed by the systemic toxic effects of
local anaesthetic should intravascular placement not be
detected. A test dose of lidocaine (to detect intrathecal
placement) and epinephrine (to detect intravascular place-
ment) is recommended in patients without contraindications
to epinephrine.
Equipment
Equipment problems may be responsible for epidural failure.
The orifice of the catheter can lie laterally or anteriorly in the
epidural space putting the local anaesthetic more to one side
and producing an unilateral block.43 In general, multi-orifice
catheters are considered better than single-orifice cathe-
ters.44 Occasionally, manufacturing errors may occur, such
as faulty markings on the epidural catheter, which can lead
to wrong depth of placement.45 Debris in the catheter or dis-
connection may similarly cause epidural failure.4 One import-
ant preventable cause for obstruction of the epidural infusion
system is an air lock, of as little as 0.3– 0.7 ml of air, in the
bacterial filter.46
Knotting of the catheter internally or externally can cause
obstruction. Only 13% of lumbar catheters inserted in a
group of 45 men were advanced more than 4 cm without
coiling, and coiling occurred at a mean insertion depth of
2.8 cm.47 Based on 18 case reports, the frequency of
knotted catheters is estimated to be 1:2000 –30 000 epidur-
als with 87% of the knots occurring ,3 cm from the tip of
the catheter and 28% of the knots were associated with a
loop in the catheter.48 Removal of a presumed knotted cath-
eter can be attempted after sensation has returned to
monitor for neurological symptoms during catheter
removal. When radicular symptoms or pain occur during
removal of a catheter, this should be immediately
Epidural anaesthesia BJA

Table 3 Comparison of various epidural doses and volumes

Study Comparison n Pain Other effects and side-effects

21
Laveaux and Bupivacaine 0.5%+4 mg ml 15/15 No difference No difference in requirement of rescue medication,
colleagues101 fentanyl vs 0.125%+1 mg ml21 respiratory depression
Snijdelaar and Bupivacaine 0.75%+4 mg ml21 30/30 No difference No difference in arterial pressure, PONV, sedation,
colleagues57 sufentanil vs 0.125%+0.7 mg ml21 respiratory depression. Significantly more rescue boli
needed by bupivacaine 0.75% group
Liu and Ropivacaine 0.2%+4 mg ml21 10/10/10 No difference No difference in PONV, pruritus, sedation, hypotension.
colleagues56 fentanyl vs 0.1%+2 mg ml21 Motor block and dosage of ropivacaine increased in the
vs 0.05%+1 mg ml21 ropivacaine 0.1%+2 mg ml21 fentanyl group. Epidural
solutions were applied via PCEA
Kampe and Ropivacaine 0.1% vs 0.2% 11/11 No difference No difference in requirement of rescue medication,
colleagues51 (+1 mg ml21 sufentanil) sensory block, motor block, patient satisfaction. More
PONV in 0.1% group
Senard and Bupivacaine 0.1% vs 0.2%; 15/15; No difference No difference in sensory block, motor block, PONV, patient
colleagues55 ropivacaine 0.1% vs 0.2% 15/15 satisfaction. Significant reduction in required dose of local
(+0.1 mg h21 morphine) anaesthetics in low-concentration groups. Local
anaesthetics were applied via PCEA, the epidural
morphine via independent constant infusion
Dernedde and Levobupivacaine 0.15% vs 0.5% 27/27 No difference No difference in requirement of rescue medication,
colleagues50 sensory block, PONV, patient satisfaction. More motor
block and lower arterial pressure in the 0.15% group
Dernedde and Levobupivacaine 0.15% vs 0.5% 26/33/31 No difference No difference in requirement of rescue analgesics, patient
colleagues49 vs 0.75% satisfaction, motor block. Sensory block two segments
higher and arterial pressure lower in 0.15% group
Dernedde and Levobupivacaine 0.15% vs 0.5% 21/20 No difference No difference in requirement of rescue medication, sensory
colleagues54 block, motor block, PONV, patient satisfaction. Marginally
(P ¼ 0.052) lower arterial pressure in 0.5% group
Sitsen and Ropivacaine 0.125% vs 0.2% 21/21 No difference No difference in patient satisfaction, motor blockade
colleagues102 (+1 mg ml21 sufentanil)
Dernedde and Levobupivacaine 0.15% vs 0.5% 30/30 No difference No difference in requirement of rescue medication,
colleagues53 sensory block, motor block, arterial pressure, heart rate,
PONV, patient satisfaction. Levobupivacaine was applied
via PCEA
Danelli and Levobupivacaine 0.75% vs 0.125% 33/32 No difference No difference in motor block, haemodynamic stability
colleagues52

stopped.4 It has been suggested that removal is easiest if the
patient is in the same position as at insertion.4 Surgical
removal of a broken catheter is not compulsory if the
patient remains asymptomatic.48
Pharmacological optimization of epidural
anaesthesia
Local anaesthetic dose vs volume
The influence of dose, concentration, and volume on the
spread of epidural anaesthesia and analgesia has undergone
considerable research, and many different volumes and con-
centrations have been assessed. In general, the main deter-
minant of epidural action is the local anaesthetic dose, with
volume playing a more minor role (Table 3). Thus, the quality
of epidural analgesia depends on total local anaesthetic dose
rather than volume or concentration, either in conventional
or patient-controlled epidural analgesia. There is a trend
towards more extended sensory block and lower arterial
pressure with lower concentrations at higher volume.49 50
Similarly, one study found a higher rate of postoperative
nausea and vomiting (PONV),51 but most studies did not
find increased side-effects.52 – 57 Dose is the primary deter-
minant of epidural anaesthesia, with volume and concentra-
tion playing a subordinate role during continuous or
patient-controlled epidural anaesthesia (PCEA) application.
The effect of volume is more pronounced during bolus appli-
cation. There is evidence supporting the role of volume in the
spread of anaesthesia. For example, the number of derma-
tomes blocked during labour analgesia was higher in a high-
volume bupivacaine group than a low-volume group when
the same total dose was given.58 However, the evidence is
equivocal. The spread of lumbar epidural anaesthesia for gy-
naecological surgery was similar with 20 ml lidocaine 1% or
10 ml lidocaine 2% was used, but the intensity of block was
higher in the 2% group.59 If the difference in volume injected
is .200% for the same concentration, the block will spread
further in the high-volume group.60 For bolus dosing, there
is evidence that reducing the dose increases the probability
of differential block. In healthy volunteers, dose-dependency
of differential block was demonstrated with bupivacaine
0.075 and 0.125%.61 Higher bupivacaine concentrations

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caused motor block. Differential block is complex and is
caused partly by differential conduction block of spinal
nerves and roots, and partly by differential central somato-
sensory integration.62
Motor block may be more extensive when performing
lumbar epidural anaesthesia because of the spatial proximity
of motor fibres.35 In labour, low-dose epidural analgesia may
be associated with fewer operative vaginal deliveries.63 The
use of a smaller dose in a higher volume has therefore
been advocated for obstetric analgesia.64
Choice of local anaesthetic
The three main long-acting local anaesthetics for epidural
anaesthesia and analgesia are bupivacaine, levobupivacaine,
and ropivacaine. Supposedly better differential block and
cardiac safety have increased the use of the newer
L-stereoisomers. The equipotency of these three drugs has
been the subject of many clinical studies. For example, equal
concentrations and dosing of bupivacaine and ropivacaine
(0.125%, with fentanyl 2 mg ml – 1) have equal analgesic effi-
cacy, but significantly less motor block in the ropivacaine
group.65 However, comparison of equal doses of, for
example, bupivacaine and ropivacaine, is difficult as the differ-
ence in potency is 40–50%.66 In assessing differential tox-
icity, this difference in potency needs to be taken into
account. The toxic threshold of local anaesthetic causing con-
vulsions in animal models66 approaches equipotency with
bupivacaine and ropivacaine if this potency difference is
included. The likelihood of successful resuscitation after local
anaesthetic toxicity is lower with bupivacaine because of pro-
longed receptor binding.67 However, lipid rescue may be more
effective for bupivacaine than ropivacaine toxicity due to the
lipophilic properties of bupivacaine.68 There is little evidence
to refute the use of bupivacaine for epidural anaesthesia or an-
algesia in adults. From the pharmacological data, changing
agents is not likely to improve epidural anaesthesia.
Addition of opioids
The addition of small doses of opioid allows for the reduction
in the local anaesthetic dose while improving the quality of
analgesia. The majority of studies support the use of a com-
bination of local anaesthetic and opioid over either drug
alone.69 A meta-analysis from 1998 showed that epidural
fentanyl was a beneficial adjuvant to local anaesthetics for
surgical analgesia, improving pain therapy and with a low in-
cidence of nausea and pruritus.70 The addition of opioids
allows for lower concentrations of local anaesthetic,
potentially reducing motor block after operation or during
labour.71 It has been suggested that the concept of
low-dose local anaesthetics for analgesia is feasible only
when adjunct opioids are used.72 Recent data suggest that
epidural opioids can enhance the suppression of the surgical
stress response.73
There are marked differences in clinical effect between
hydrophilic opioids, such as morphine, and lipophilic
opioids, such as fentanyl and sufentanil. Microdialysis
150
Hermanides et al.
studies show that epidural morphine has a longer residence
time in the epidural space, and results in higher CSF concen-
trations compared with sufentanil or fentanyl.74 This longer
residence time results in a spinal mechanism of action, and
consequently, a substantial reduction in morphine dose
required epidurally compared with i.v.75 The evidence for
lipophilic opioids such as fentanyl and sufentanil, however,
is conflicting. While some studies show a clear benefit of
adding epidural fentanyl to bupivacaine,76 others suggest
that effects of epidural fentanyl are primarily mediated
by supraspinal mechanisms after systemic absorption.77
A recent study in healthy volunteers found differences
between continuous and bolus infusion. While continuous in-
fusion resulted in non-segmental analgesia, indicating a
supraspinal action, bolus injection resulted in segmental an-
algesia which indicates a significant spinal contribution.76
Therefore, a spinal analgesic mechanism may depend on suf-
ficient concentrations of fentanyl in the epidural space to
allow diffusion into the CSF. This has been estimated to be
.10 mg ml21, which is greater than most current post-
operative analgesia regimens.78
There are some potential disadvantages of epidural opioid
administration. First, the safety of opioids in obstetric anal-
gesia has been questioned and include possible interference
with breastfeeding.79 However, a recent RCT found no effect
of epidural fentanyl on breastfeeding initiation or duration.80
Secondly, biphasic respiratory depression may occur when
hydrophilic opioids are given epidurally. With hydrophilic
opioids such as morphine, the first peak corresponds to ab-
sorption from the epidural space into the systemic circulation
and occurs 30–90 min after injection, while the second
occurs 6–18 h later as morphine spreads towards the brain-
stem. With lipophilic opioids, there is only early depression
due to absorption and rostral spread.81
Addition of epinephrine
The addition of epinephrine to epidural solutions has two
useful effects. First, vasoconstriction causes delayed absorp-
tion of local anaesthetic into the systemic circulation, with
higher effect-site and lower plasma concentrations. Second-
ly, epinephrine has specific antinociceptive properties pre-
dominantly mediated via a-2 adrenoreceptors. The effects
of epinephrine on local anaesthetics and opioids are additive.
For example, the minimum local anaesthetic concentration
(MLAC) of bupivacaine is reduced by 29% in labouring parturi-
ents.82 Adding epinephrine to a low-dose thoracic epidural
infusion of ropivacaine and fentanyl improved pain relief
and reduced nausea.83
Vasoconstriction plays a key role in the effect of epineph-
rine on epidural analgesia. Amide-type local anaesthetics are
not metabolized in the epidural space and the main deter-
minant for their concentration is absorption into the systemic
circulation and subsequent hepatic metabolism. This absorp-
tion is biphasic, with an initial fast peak reflecting the fluid
phase and later a slower second peak corresponding to re-
sorption from the lipid compartment.84 The addition of
Epidural anaesthesia
epinephrine to local anaesthetic solutions slows the first
phase.85 The net clinical effect is a more profound block, or
a lower dose requirement. The same mechanism seems to
apply to opioids.86
Epidural epinephrine has a specific a-2-mediated antino-
ciceptive effect causing decreased presynaptic transmitter
release and postsynaptic hyperpolarization within the sub-
stantia gelatinosa of the spinal cord dorsal horn.87 Therefore,
the full effect is only observed when the epidural catheter is
positioned close to the spinal cord, that is, above L1. Lumbar
catheters require higher concentrations of local anaesthetic
and opioid, and here, adding epinephrine may increase the
risk of motor block.87 Studies suggest a concentration of
1.5–2 mg ml21.88
Some potential risks of adding epinephrine include
causing longer labour, and decreased uterine blood flow.89
At doses used clinically, spinal cord ischaemia seems not
to be a clinically significant problem.90
Bolus vs continuous dosing
The use of PCEA has profoundly changed postoperative
pain management. In labour analgesia, a meta-analysis
demonstrated that obstetric patients using PCEA needed
less co-analgesic interventions, less local anaesthetic, and
decreased likelihood of motor block. However, there was no
difference in maternal satisfaction or mode of delivery.91
There is conflicting evidence on the benefit of background
infusions when pain scores and cumulative local anaesthetic
dose are used as a measure of outcome. PCEA requirements
are determined by the site of surgery, surgery for malignant
disease, and also patient weight and age.92 The addition of a
continuous infusion to PCEA during labour resulted in
reduced total dose of local anaesthetic while providing ef-
fective analgesia.93 A reduction in local anaesthetic dose
was found only in demand-only PCEA, but not with back-
ground infusion by Vallejo and colleagues,94 despite similar
outcomes. Demand-only PCEA resulted in lower local anaes-
thetic requirement, but also in more breakthrough pain,
higher pain scores, and lower maternal satisfaction during
labour.95 More refined techniques such as programmed inter-
mittent epidural bolus combined with PCEA have shown
potential.96
Conclusion
In conclusion, failure of epidural anaesthesia and analgesia
occurs in up to 30% in clinical practice. Some technical
factors can help to increase the primary and secondary
success rate. Epidural catheters may be incorrectly placed,
or may migrate after initial correct placement due to body
movement and oscillations in CSF. Catheters may deviate
from the midline during insertion. The optimal depth of inser-
tion in adults is 5 cm. The most widely used method with
the least side-effects for localizing the epidural space is
LoR to saline. None of the additional technical tools available
has sufficient accuracy and predictability to justify routine
use, but there is a growing evidence-base for ultrasound in
BJA
obese patients and infants. The optimal test dose should
combine lidocaine and epinephrine, to detect intrathecal
and intravascular placement, respectively. The choice of
long-acting local anaesthetic agent seems to be less import-
ant clinically. Dose is the primary determinant of continuous
epidural anaesthesia, with volume and concentration playing
a subordinate role. Addition of opioids may substantially in-
crease the effectiveness of epidural analgesia. Epinephrine
augments analgesia by delaying resorption of local anaes-
thetic from the epidural space, and by direct antinociceptive
action at the spinal cord. The use of patient-controlled epi-
dural analgesia with background infusion appears to be the
best method for postoperative analgesia.
Declaration of interest
None declared.
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